The central goal of this research is a better understanding of the pathophysiology of stroke. The major effort is directed toward developing and implementing better quantitative methods to enable study of important pathophysiologic mechanisms, correlating these with quantitative morphology, mathematical modeling and computer simulation. The projects include perfection of the 133 senon inhalation method for rCBF and with it to explore the hypothesis that the circulation is mainly the servant of the brain parenchyma, utilizing the technique of intellectual activation of blood flow; utilization of a variety of electochemical and electrophysiologic measurements of local flow, metabolism, and function to predict in vivo the pathologic state of the tissue in experimental cerebral infarction; analysis of the memebrane events leading to irreversible hypoxic depolarization of the Aplysia neurone; study of blood and tissue factors which impede microflow.